SU898956A3 - Method of preparing benzo (b) thiophene-2 derivatives or their salts - Google Patents

Abstract

Oxothia compounds, especially 2-oxo-2,3-dihydro-benzo[b]-thiophene compounds of the formula <IMAGE> (I) in which Ph represents an optionally substituted 1,2-phenylene radical, X represents oxygen or sulphur, R1 represents an organic radical bonded via a carbon atom and R2 denotes hydrogen or an optionally substituted hydrocarbon radical of aliphatic character, and their salts are useful as peripheral analgetics and/or as antiphlogistic uricosuric and/or thrombolytic agents.

Description

38 where R, X and X have the above values, they are reacted with dibromal kan of the general formula BrCHR (CH2) cBr, where B / (And n have the indicated values, followed by treatment with fl J amine. However, in the literature, there are no pharmacologically active benzo derivatives in thiophenone-2 of general formula 1 or their salts. The purpose of the invention is to develop a method for producing benzo [derivatives] in thiophenone-2 of general formula 1 or their salts with valuable properties. The goal is achieved by the described method of producing benzo-1-thiophenone-2 of the general formula 1 or their salts, consisting in that the compound of the general formula O-Co, r CH 2 NR R O SH where R, R and R have the above-mentioned values subjected to cyclization with and, if necessary, in the presence of acid, followed by isolation of the target product in free form or as a salt. Compounds of general formula 1 exhibit peripheral analgesic and anti-inflammatory effects. These compounds also have a uricosuric and antithrombotic effect. Therefore, they can be used for the treatment of arthritis, gout and as thrombolytic agents. Example 1. 7,7-Diamide-M, (3 chloranyl.id) 2- (o-mercapto-phenylmalonic acid is dissolved in 50 ml of dimethyl sulfoxide, 0.5 g of concentrated sulfuric acid is added and stirred overnight at 50 ° C. To the reaction mixture are added 100 ml of diethyl ether and washed first with a dilute sodium hydroxide solution and then with water, dried with sodium sulfate, evaporated, chromatographed on silica gel and recrystallized from ether to give N- (3-chloro-feiyl) -2-oxo-2,3 -benzo {in thiophene-carboxamide, mp 175-176 ,. This compound is also obtained from 2- (o-mer aptophenyl) malonyl chloride-N- (3-chloroanilide), which is heated with chlorosulfonic acid in tetrahydrofuran for 3 hours to 150 ° C, and the resulting N- (3-chloroanilide) methyl 2- (o-mercaptophenyl) -malonic acid ester is heated in acetamide for 3 hours at 120 ° C, after the treatment of the reaction mixture described above, N- (3-chlorophenyl) -2-oxo-2,3-benzo in thiophene-carboxamide is obtained. Under similar conditions, the following compounds of the general formula 1: N- ( 2, dichlorophenyl) -2-oxo-2,3-dihydro-3-ben3o to thiophenecarboxamide, with Topl. 201-203 C; N- (4-methoxyphenyl) -2-oxo-2,3-dihydro-3-benzo in thiophenecarboxamide, G m.p. „181-183 ° С; N- (2-methylphenyl) -2-oxo-2,3 dihydro-3 benzo in thiophenecarboxamide with Topl. 153-155 ° C; N- (3,5-bistrifluoromethylphenyl) -2-oxo-2, 3-dihydro-3-benzo in -thiophencarboxamide with m.p., 1b9-171 ° C; H - (- Methylphenyl) -2-oxo-2,3-dihydro-3 benzo in thiophenecarboxamide with | T. mp. 17b-179C; N - (- ethoxyphenyl) -2-OXO-2, 3-dihydro-3 benzo in thiophencarboxamide with so pl. HS-ISI C; N- (4-bromophenyl) -2-OXO-2,3-Dihydro-3 6eH3of in thiophencarboxamide with so pl. 178-180 ° C; N- (3 (Zmethylisoxazolyl) -2 oxo-2, 3 DIGIDRO-2-benzo in thiophenylcarboxamide with m.p. ISt-lSo C; N- (2-methoxycarbonylphenyl) -2-oxo-2, 3 Dihydro-3-benzo in thiophenecarboxamide with m.pl., and also by hydrolysis of the latter: N- (2-carboxyphenyl) -2-oxo-2,3-di-hydro-3-benzo to thiophenecarboxamide, N (3, 4-dimethoxyphenyl) -2- oxo-2, 3-dihydro-3 benzo in thiophenecarboxamide with m „PL. ISt-ISG C; N- (2-methoxyphenyl) -2-oxo-2,3-dihydro 3-benzo in thiophene carboxamide with mp 1itO -U2C; N (3 Dichlorophenyl) -2-oxo-2,3-dihydro-3 benzo in thiophenecarboxamide with mp 192-19 ° C; M-butyl-2,3-Dihydro-2-oxo-3- benzo in thiophenecarboxamide; H- enzil-2, Z-dihydro-2-oxo-benzo into thiophenecarboxamide;

N- (Zhporpenil) -5-chloro-2,3-dihydro-2-oxo-6enzo in thiophenecarboxamide with so pl. 1bO-1bZS;

N- (2-thiazolyl) -5 chloro-2.3 dihydro-2-oxo-benzo-1 thiophene carboxamide with a temperature of 29b-299 ° C;

N-phenyl-5 chloro-2,3 dihydro-2-oxo-benzo in thiophene-carboxamide with tpl 170-1724;

N- (-ethoxyphenyl) -5-chloro-2, 3-DiHydro-2-oxo-3-benzo in thiophenecarboxamide, mp: 202-205С;

N- (2-fluorophenyl) -5-chloro-2,3-dihydro-2-oxo-3-benzo in thiophencarboxes with Topl. 205-207С;

M-phenyl-5-carboxy-2,3 dihydro-2-oxo-3-benzo to thiophenecarboxamide;

N- (2-methylphenyl) -5 carboxy-2,3-dihydro-2-oxo-3-benzo | in thiophencarboxamide;

N- (2-methylphenyl) -5-carboxy-2,3-dihydro-2-oxo-3-benzoHv thiophenecarboxamide;

N- (2-chlorophenyl) -5-carboxy-2,3-dihydro-2-oxo-2-benzo to thiophenecarboxamide;

N- (3 chlorophenyl) -5 carboxy-2,3-di hydro-2-oxo-3-benzo to thiophenecarboxamide, as well as their methyl ester;

M- (2-phtarphenyl) -6-chloro-2,3-Dihydro-2-oxo-3-benzo in 3thiofencarboxes with mp of 187-190 ° C;

H-phenyl-6-chloro-2, 3-dihydro-2-oxo-3-benzo-1-thiophene-carboxamide with m.p., 01-20if C;

N- (3-chlorophenyl) -b-chloro-2,3-dihydro-2-oxo-3-benzo in thiophencarboxes with m „PL, 212-215 ° C;

N -. {2-chlorophenyl) -6-chloro-2,3-dihydro-2-oxo-3-benzo in thiophencarboxes with m pl 1b9-170C;

M-phenyl-2,3-dihydro-6-methoxy-2-oxo-3-benzo | in thiophencarboxamide;

N- (2-chlorophenyl) -2, 3-diHydro-6-methoxy-2-oxo-3 6-benzo-Hl thiophene carboxamide;

N- (3 chlorophenyl) -2,3-dihydro-6-methoxy-2-oxo-3-benzoHv thiophenecarboxamide;

M- (2-Fluorophenyl) -2,3-Dyhydro-6-methoxy-2-oxo-3-Benzo-b-thiofenccarbamide;

N- (2-fluorophenyl) -2,3-dihydro-6-hmethoxy-2-oxo-3-benzo in IT iofencarboxamide;

N-phenyl-2,3 dihydro-5-nitro-2-oxo-3 benzo to thiophenecarboxamide;

N- (2-chlorophenyl) -2,3-dihydro-5-nitro-2-oxo-3-benzo to thiophenecarboxamide;

N- (Z-chlorophenyl) -2,3 Dihydro-5-nitro-2-oxo-3-benzo to thiophenecarboxamide;

N- (2-fluorophenyl) -2, 3-dihydro-5-nitro-2-oxo-3-benzoV in thiophencarboxamide.

Take p2. To a boiling suspension of 7 g of M- (3-chlorophenyl) -2-oxo-2,3-dihydro-3-benzoGv thiophenecarboxamide in 200 ml of acetone was added 2 ml of morpholine, and the entire suspension was dissolved. The clear solution is cooled and diluted with 250 ml of petroleum ether, the morpholine salt of M- (3-chlorophenyl) -2-oxo-2,3 dihydro-3-benzoic crystallizes in thiophene-carboxamide, which is filtered and dried, mp: 1 72-1 73, C.

Example 3. 2.2 g of M- (3-chlorophenyl) -2-OXO-2, 3 Dihydro-3-benzo c} thiophene carboxamide is heated moderately in a mixture of 7.5 ml 1 But sodium hydroxide solution and 30 ml of water, moreover at a temperature of about everything is dissolved, 1.1 g of zinc sulfate heptahydrate in 5 ml of WATER is added to the solution, filtered after 30 minutes. crystalline precipitate of zinc salt of N- (Z-chlorophenyl) -2-OXO-2,3 dihydro-3 benzo | in thiofencarboxamide and dry it. Salt has a melting point of about 172 ° C (with evolution of gas).

Example A. 20 g of N- (3-chlorophenyl) -2-OXO-2,3-dihydro-3-benzo-b-thiophene-carboxamide are suspended in 250 ml of acetone and mixed with 6.6 N sodium hydroxide solution, after which a solution is formed. It is evaporated to dryness, the residue after evaporation is stirred first with toluene, and then with diethyl ether, sucked off, and dried. The sodium salt of N- (3-chlorophenyl) -2-oxo-2,3-diHydro-3-benzo-1-thiophene-carboxamide is obtained with Topl. above .

Claims (1)

Invention Formula Method for producing benzo derivatives | in thiophenone-2 of general formula 1 where R is hydrogen, alkyl. with 1-7. carbon atoms, alkoxy 1 group with 1-7 carbon atoms, alkoxycarboyl with 2-8 carbon atoms, carboxy or nitro group or halogen; Ri / - alkyl with 1-7 carbon atoms phenyl, unsubstituted or substituted by alkyl with 1-7 carbohydrate atoms, alkoxy group with 1-7 carbon atoms, alkoxycarbonyl with 2-8 carbon atoms, carboxy, nitro, trifluoro methyl group or halogen pyridyl, thienyl, thiazolyl, or isoxol zolyl, unsubstituted or substituted by alkyl with 1 - carbon atoms; R2 is hydrogen or alkyl with 1-7 carbon atoms, or their salts, characterized in that the compound of the general formula 11; OrCRj CHCNR.Rj where K, R. and R- have the above values; RT is a lower alkoxy group, halogen, anilino group is replaced by halogen. subjected to cyclization at 50-180C and, if necessary, in the presence of acid, followed by separation of the target product in free form or in the form of a salt. . Priority on the grounds: .7b with R - hydrogen, alkyl with 1-7 carbon atoms, alkoxy group with 1-7 carbon atoms, nitro group or halogen; R is as defined in the claims, other than thienyl; R is as defined in the claims, in free form. 20,12.76. At R - hydrogen, alkyl with 1-7 carbon atoms, alkoxy group with 1-7 carbon atoms, nitro group or halogen; R is as defined in the claims, other than thienyl; R2 is as defined in the claims, in the form of a salt. Vol.02 „78 (Filing date of application). R, R and R 2 have the meanings indicated in the claims, in free form or in salt. Sources of information taken into account in the examination 1. USSR Author's Certificate no. C 07 O 333/56, 1972 /